Cargando…

De Novo Design of κ-Opioid Receptor Antagonists Using a Generative Deep-Learning Framework

[Image: see text] Likely effective pharmacological interventions for the treatment of opioid addiction include attempts to attenuate brain reward deficits during periods of abstinence. Pharmacological blockade of the κ-opioid receptor (KOR) has been shown to abolish brain reward deficits in rodents...

Descripción completa

Detalles Bibliográficos
Autores principales:	Salas-Estrada, Leslie, Provasi, Davide, Qiu, Xing, Kaniskan, Husnu Ümit, Huang, Xi-Ping, DiBerto, Jeffrey F., Lamim Ribeiro, João Marcelo, Jin, Jian, Roth, Bryan L., Filizola, Marta
Formato:	Online Artículo Texto
Lenguaje:	English
Publicado:	American Chemical Society 2023
Acceso en línea:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10466374/ https://www.ncbi.nlm.nih.gov/pubmed/37555591 http://dx.doi.org/10.1021/acs.jcim.3c00651

Ejemplares similares

A combination of machine learning and infrequent metadynamics to efficiently predict kinetic rates, transition states, and molecular determinants of drug dissociation from G protein-coupled receptors
por: Lamim Ribeiro, João Marcelo, et al.
Publicado: (2020)

Insights From Molecular Dynamics Simulations of a Number of G-Protein Coupled Receptor Targets for the Treatment of Pain and Opioid Use Disorders
por: Ribeiro, João Marcelo Lamim, et al.
Publicado: (2019)

Atomic-Level Characterization of the Methadone-Stabilized Active Conformation of µ-Opioid Receptor
por: Kapoor, Abhijeet, et al.
Publicado: (2020)

Differences in interactions between transmembrane domains tune the activation of metabotropic glutamate receptors
por: Thibado, Jordana K, et al.
Publicado: (2021)

Lessons from Free Energy Simulations of δ-Opioid Receptor Homodimers Involving the Fourth Transmembrane Helix
por: Provasi, Davide, et al.
Publicado: (2010)

Agonist and antagonist TRUPATH assays for G protein-coupled receptors
por: DiBerto, Jeffrey F., et al.
Publicado: (2022)

Preferred Supramolecular Organization and Dimer Interfaces of Opioid Receptors from Simulated Self-Association
por: Provasi, Davide, et al.
Publicado: (2015)

Dynamic and Kinetic Elements of µ-Opioid Receptor Functional Selectivity
por: Kapoor, Abhijeet, et al.
Publicado: (2017)

Impact of Lipid Composition and Receptor Conformation on the Spatio-temporal Organization of μ-Opioid Receptors in a Multi-component Plasma Membrane Model
por: Marino, Kristen A., et al.
Publicado: (2016)

Proposed Mode of Binding and Action of Positive Allosteric Modulators at Opioid Receptors
por: Shang, Yi, et al.
Publicado: (2016)

Kinetic and thermodynamic insights into sodium ion translocation through the μ-opioid receptor from molecular dynamics and machine learning analysis
por: Hu, Xiaohu, et al.
Publicado: (2019)

An efficient strategy to estimate thermodynamics and kinetics of G protein-coupled receptor activation using metadynamics and maximum caliber
por: Meral, Derya, et al.
Publicado: (2018)

Molecular details of dimerization kinetics reveal negligible populations of transient µ-opioid receptor homodimers at physiological concentrations
por: Meral, Derya, et al.
Publicado: (2018)

Making Structural Sense of Dimerization Interfaces of Delta Opioid Receptor Homodimers
por: Johnston, Jennifer M., et al.
Publicado: (2011)

Assessing the Relative Stability of Dimer Interfaces in G Protein-Coupled Receptors
por: Johnston, Jennifer M., et al.
Publicado: (2012)

Metadynamics simulations leveraged by statistical analyses and artificial intelligence-based tools to inform the discovery of G protein-coupled receptor ligands
por: Salas-Estrada, Leslie, et al.
Publicado: (2022)

Selective κ Opioid Antagonists nor-BNI, GNTI and JDTic Have Low Affinities for Non-Opioid Receptors and Transporters
por: Munro, Thomas A., et al.
Publicado: (2013)

Ligand-Induced Modulation of the Free-Energy Landscape of G Protein-Coupled Receptors Explored by Adaptive Biasing Techniques
por: Provasi, Davide, et al.
Publicado: (2011)

Gαs slow conformational transition upon GTP binding and a novel Gαs regulator
por: Ahn, Donghoon, et al.
Publicado: (2023)

Stilbenes as κ-Selective, Non-nitrogenous Opioid Receptor Antagonists
por: Hartung, Alyssa M., et al.
Publicado: (2014)

Chemical Probes of Histone Lysine Methyltransferases
por: Kaniskan, H. Ümit, et al.
Publicado: (2014)

Targeting opioid receptor signaling in depression: do we need selective κ opioid receptor antagonists?
por: Bailey, Sarah J., et al.
Publicado: (2018)

Structural Insights into the Unexpected Agonism of Tetracyclic Antidepressants at Serotonin Receptors 5-HT1eR and 5-HT1FR
por: Zilberg, Gregory, et al.
Publicado: (2023)

Differential Stability of the Crystallographic Interfaces of Mu- and Kappa-Opioid Receptors
por: Johnston, Jennifer M., et al.
Publicado: (2014)

Nanobody-enabled monitoring of kappa opioid receptor states
por: Che, Tao, et al.
Publicado: (2020)

Targeted Degradation of PRC1 Components, BMI1 and RING1B, via a Novel Protein Complex Degrader Strategy
por: Park, Kwang‐Su, et al.
Publicado: (2023)

Selective Inhibitors of Protein Methyltransferases
por: Kaniskan, H. Ümit, et al.
Publicado: (2014)

Inhibitors of Protein Methyltransferases and Demethylases
por: Kaniskan, H. Ümit, et al.
Publicado: (2017)

Long-acting κ opioid antagonists nor-BNI, GNTI and JDTic: pharmacokinetics in mice and lipophilicity
por: Munro, Thomas A, et al.
Publicado: (2012)

Past–future information bottleneck for sampling molecular reaction coordinate simultaneously with thermodynamics and kinetics
por: Wang, Yihang, et al.
Publicado: (2019)

Development of a Selective Peptide κ-Opioid Receptor Antagonist by Late-Stage Functionalization with Cysteine Staples
por: Muratspahić, Edin, et al.
Publicado: (2023)

Opioids in cancer: The κ-opioid receptor
por: Zhou, Qier, et al.
Publicado: (2022)

Abuse Potential and Pharmacodynamic Characteristics of Oral and Intranasal Eluxadoline, a Mixed μ- and κ-Opioid Receptor Agonist and δ-Opioid Receptor Antagonist
por: Levy-Cooperman, N., et al.
Publicado: (2016)

Increasingly powerful opioid antagonists are not necessary
por: Hill, Lucas G., et al.
Publicado: (2022)

Opioid Antagonist in the Treatment of Ischemic Stroke
por: Ortiz, Juan Fernando, et al.
Publicado: (2021)

Metabolic clearance of select opioids and opioid antagonists using hepatic spheroids and recombinant cytochrome P450 enzymes
por: Tuet, Wing Y., et al.
Publicado: (2022)

Mechanistic Insights into the Allosteric Modulation of Opioid Receptors by Sodium Ions
por: Shang, Yi, et al.
Publicado: (2014)

Opioid Antagonists from the Orvinol Series as Potential Reversal Agents for Opioid Overdose
por: Disney, Alex, et al.
Publicado: (2022)

Biased Opioid Antagonists as Modulators of Opioid Dependence: Opportunities to Improve Pain Therapy and Opioid Use Management
por: Sadee, Wolfgang, et al.
Publicado: (2020)

μ Opioid receptor: novel antagonists and structural modeling
por: Kaserer, Teresa, et al.
Publicado: (2016)

Cannot write session to /tmp/vufind_sessions/sess_7r07s65rqd2c52p7o4d59kkmb1